title: Hes1 expression and CYLD repression are essential events downstream of Notch1 in T-cell leukemia.
abstract: Notch activation is a current event in T Acute Lymphoblastic Leukemia (T-ALL) but the downstream elements that are able to support Notch-dependent leukemias are not well characterized. We have recently shown that the Notch-Hes1-CYLD-NFkB axis is crucial in the maintenance of T-ALL, but detailed evaluation of the contribution of each one of these elements is still missing. Here we use a Notch1-induced leukemia in vivo model to study the effect of silencing the Notch-target gene, Hes1, or over-expressing the Hes1-target, CYLD. We here show that both strategies completely abolish the ability of constitutive active Notch1 to generate T-ALL.
authors.affiliation: Parc Recerca Biomèdica de Barcelona; Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: D'Altri
authors.forename: Jessica
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Iannis
authors.initials: I
authors.lastname: Aifantis
authors.forename: Lluis
authors.initials: L
authors.lastname: Espinosa
authors.forename: Anna
authors.initials: A
authors.lastname: Bigas
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D000074749:Deubiquitinating Enzyme CYLD; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D015458:Leukemia, T-Cell / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072056:Transcription Factor HES-1; D014161:Transduction, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003546:Cysteine Endopeptidases; D017931:DNA Primers; D000074749:Deubiquitinating Enzyme CYLD; D018398:Homeodomain Proteins; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C511601:CYLD protein, mouse